Sd. Ginsberg et al., SEQUESTRATION OF RNA IN ALZHEIMERS-DISEASE NEUROFIBRILLARY TANGLES AND SENILE PLAQUES, Annals of neurology, 41(2), 1997, pp. 200-209
The polypeptide composition of neurofibrillary tangles (NFTs) and seni
le plaques (SPs) has been characterized extensively within the Alzheim
er's disease (AD) brain. Because few data exist on the nonproteinaceou
s components of these lesions, we sought to determine if NFTs, neuropi
l threads (NTs), and SPs contain RNA species. To accomplish this, acri
dine orange (AO) histofluorescence was employed, alone or in combinati
on with thioflavine S (TS) staining and immunohistochemistry to identi
fy RNAs in paraffin-embedded tissue sections of hippocampus and entorh
inal cortex. Postmortem brain samples came from 32 subjects including
AD and elderly Down's syndrome (DS) patients, age-matched normal contr
ols, and non-AD diseased controls. AO stained the cytoplasm of normal
hippocampal and entorhinal neurons in all of the cases, while NFTs, NT
s, and SPs were AO-positive in the same regions of AD and DS brains. C
ytoplasmic AO histofluorescence was abolished with RNase, but not DNas
e or proteinase K, indicating the relative specificity of AO for RNA s
pecies. Quantitative analysis of double-labeled sections demonstrated
that approximately 80% of TS-positive NFTs also were AO-positive, wher
eas approximately 55% of TS-stained SPs contained AO labeling. These n
ovel observations demonstrate the presence of RNAs in NFTs, NTs, and S
Ps.